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Myeloid derived suppressor cells

E Fehri, E Ennaifer, R Bel Haj Rhouma, L Guizani-Tabbane, I Guizani, S Boubaker
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis...
July 2016: Current Research in Translational Medicine
Xing-Hui Gao, Lu Tian, Jiong Wu, Xiao-Lu Ma, Chun-Yan Zhang, Yan Zhou, Yun-Fan Sun, Bo Hu, Shuang-Jian Qiu, Jian Zhou, Jia Fan, Wei Guo, Xin-Rong Yang
BACKGROUND AND AIM: Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression. The aim of the present study was to investigate the prognostic value of MDSCs for early recurrence of hepatocellular carcinoma (HCC) patients undergoing curative resection. METHODS: MDSCs were measured by flow cytometry. The correlation between MDSCs and tumor recurrence were analyzed using a cohort of 183 patients who underwent curative resection between February 2014 and July 2015...
October 20, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
O Lidický, M Šírová, T Etrych
In this paper, we describe the synthesis, physicochemical characterization, drug release kinetics and preliminary biological evaluation of several N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer-retinoid conjugates designed for solid tumor immunotherapy. The conjugates are supposed to inhibit the immunosuppressive activity of myeloid-derived suppressor cells (MDSC) accumulated in the solid tumor microenvironment. All-trans retinoic acid (ATRA) was derivatized to hydrazide (AtrHy) and then attached to the polymer backbone via a spacer that is stable at the normal pH of blood (7...
October 20, 2016: Physiological Research
Shu Wen Wen, Jaclyn Sceneay, Luize G Lima, Christina Sf Wong, Melanie Becker, Sophie Krumeich, Richard J Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S Parker, Andreas Moller
Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here we use optical imaging to determine that exogenously administered fluorescently-labeled exosomes derived from highly metastatic murine breast cancer cells, distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45+ bone marrow-derived cells...
October 19, 2016: Cancer Research
Prashant Trikha, Robert L Plews, Andrew Stiff, Shalini Gautam, Vincent Hsu, David Abood, Robert Wesolowski, Ian Landi, Xiaokui Mo, John Phay, Ching-Shih Chen, John Byrd, Michael Caligiuri, Susheela Tridandapani, William Carson
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of early myeloid cells that accumulate in the blood and tumors of patients with cancer. MDSC play a critical role during tumor evasion and promote immune suppression through variety of mechanisms, such as the generation of reactive oxygen and nitrogen species (ROS and RNS) and cytokines. AMPactivated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis and metabolic stress. However, the role of AMPK in the regulation of MDSC function remains largely unexplored...
2016: Oncoimmunology
Jie Qin, Yusuke Arakawa, Miwa Morita, John J Fung, Shiguang Qian, Lina Lu
BACKGROUND: Islet transplantation is a promising therapeutic approach for restore the physical response to blood glucose in type 1 diabetes. Current chronic use of immunosuppressive reagents for preventing islet allograft rejection is associated with severe complications. In addition, many of the immunosuppressive drugs are diabetogenic. The induction of transplant tolerance to eliminate the dependency on immunosuppression is ideal, but remains challenging. METHODS: Addition of hepatic stellate cells allowed generation of myeloid-derived suppressor cells (MDSC) from precursors in mouse bone marrow...
October 17, 2016: Transplantation
Jun P Ren, Lin Wang, Juan Zhao, Ling Wang, Shun B Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
Myeloid-derived suppressor cells (MDSCs) and microRNAs (miRNAs) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSCs that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus (HCV) infection. Here we further investigated whether the HCV-induced expansion of MDSCs and Tregs is regulated by a miRNA-mediated mechanism...
October 18, 2016: Immunology
Xin Long, Jian Wang, Jian-Ping Zhao, Hui-Fang Liang, Peng Zhu, Qi Cheng, Qian Chen, Yan-Hui Wu, Zhan-Guo Zhang, Bi-Xiang Zhang, Xiao-Ping Chen
The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group)...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Jingwei Jiang, Qingmin Gao, Tian Wang, Hao Lin, Qiong Zhan, Zhaohui Chu, Ruofan Huang, Xinli Zhou, Xiaohua Liang, Weijian Guo
Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that can suppress antitumor immunity. MDSCs are divided into granulocytic (G‑MDSCs) and monocytic subsets. In the present study, the microRNA profiles of the G‑MDSCs were determined and the differential expression of microRNAs between G‑MDSCs from tumor‑bearing mice and tumor‑free mice was examined. The number of G‑MDSCs in spleens of Lewis lung carcinoma (LLC)‑bearing mice was ~6‑fold higher than in spleens of normal mice (13...
October 13, 2016: Molecular Medicine Reports
Lucia Geis-Asteggiante, Suzanne Ostrand-Rosenberg, Catherine Fenselau, Nathan J Edwards
Spectral counting is a straightforward label-free quantitation strategy used in bottom-up proteomics workflows. The application of spectral counting in label-free top-down proteomics workflows can be similarly straightforward, but has not been applied as widely as quantitation by chromatographic peak areas or peak intensities. In this study, we evaluate spectral counting for quantitative comparisons in label-free top-down proteomics workflows by comparison with chromatographic peak areas and intensities. We tested these quantitation approaches by spiking standard proteins into a complex protein background and comparing relative quantitation by spectral counts with normalized chromatographic peak areas and peak intensities from deconvoluted extracted ion chromatograms of the spiked proteins...
October 17, 2016: Analytical Chemistry
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Shu-Hong Wang, Qing-Yang Lu, Ya-Huan Guo, Yuan-Yuan Song, Pei-Jun Liu, Yao-Chun Wang
Myeloid-derived suppressor cells (MDSCs) mostly consisting of polymorphonuclear (PMN)-MDSCs and mononuclear MDSCs have been considered to play critical roles in immunosuppression, angiogenesis, invasion and metastases of various tumours. However, it is still unclear the regulated mechanisms underlying the generation and immunosuppression of two major MDSC subsets. Here, we report Notch signalling was inhibited significantly in tumour-bearing mouse MDSCs, in which PMN-MDSCs were the major population. MDSCs without recombination signal binding protein-Jк (RBP-J), the critical transcription factor mediating signalling from all four mammalian Notch receptors, reduced their ability of inhibiting the proliferation and activation of allogenic T cells...
October 8, 2016: European Journal of Cancer
Sitara Chauhan, Steven Danielson, Virginia Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Catherine Fenselau
In this report we use a proteomic strategy to identify glycoproteins on the surface of exosomes derived from myeloid-derived suppressor cells (MDSC), and then test if selected glycoproteins contribute to exosome-mediated chemotaxis and migration of MDSC. We report successful modification of a surface chemistry method for use with exosomes, and identify twenty-one surface N-glycoproteins on exosomes released by mouse mammary carcinoma-induced MDSC. These glycoprotein identities and functionalities are compared with ninty-three N-linked glycoproteins identified on the surface of the parental cells...
October 11, 2016: Journal of Proteome Research
Roni Allaoui, Caroline Bergenfelz, Sofie Mohlin, Catharina Hagerling, Kiarash Salari, Zena Werb, Robin L Anderson, Stephen P Ethier, Karin Jirström, Sven Påhlman, Daniel Bexell, Balázs Tahin, Martin E Johansson, Christer Larsson, Karin Leandersson
Triple-negative (TN) breast cancers (ER(-)PR(-)HER2(-)) are highly metastatic and associated with poor prognosis. Within this subtype, invasive, stroma-rich tumours with infiltration of inflammatory cells are even more aggressive. The effect of myeloid cells on reactive stroma formation in TN breast cancer is largely unknown. Here, we show that primary human monocytes have a survival advantage, proliferate in vivo and develop into immunosuppressive myeloid cells expressing the myeloid-derived suppressor cell marker S100A9 only in a TN breast cancer environment...
October 11, 2016: Nature Communications
Hoibin Jeong, Seoyeon Bok, Beom-Ju Hong, Hyung-Seok Choi, G-One Ahn
Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation...
September 2016: Blood Research
H Zhang, Y-L Ye, M-X Li, S-B Ye, W-R Huang, T-T Cai, J He, J-Y Peng, T-H Duan, J Cui, X-S Zhang, F-J Zhou, R-F Wang, J Li
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33(+) MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0...
October 10, 2016: Oncogene
A K A Wright, C Newby, R A Hartley, V Mistry, S Gupta, R Berair, K M Roach, R Saunders, T Thornton, M Shelley, K Edwards, B Barker, C E Brightling
BACKGROUND: The role of fibrocytes in COPD is unknown. We sought to enumerate blood and tissue fibrocytes in COPD and determine the association of blood fibrocytes with clinical features of disease. METHODS: Utilising flow cytometry to identify circulating, collagen type-1(+) cells we found two populations 1) CD45(+) CD34(+) (fibrocytes) and 2) CD45(+) CD34(-) (myeloid-derived suppressor cell [MDSC]-like fibrocytes) cells in stable COPD (n=41) and control (n=29) subjects...
October 6, 2016: Allergy
Mary Francis, Richard Sun, Jessica A Cervelli, Hyejeong Choi, Mili Mandal, Elena V Abramova, Andrew J Gow, Jeffrey D Laskin, Debra L Laskin
Macrophages and inflammatory mediators have been implicated in ozone toxicity. In these studies, we used splenectomized (SPX) mice to assess the contribution of splenic monocytes to pulmonary inflammation and injury induced by ozone. Cells and tissue were collected 24-72 h after exposure of mice to air or ozone (0.8 ppm, 3 h). Following ozone exposure, increased numbers of pro-inflammatory CD11b(+)Ly6C(Hi) and anti-inflammatory CD11b(+)Ly6C(Lo) monocytes were observed in spleens of control (CTL) mice. CD11b(+)Ly6C(Hi) and MMP-9(+) pro-inflammatory macrophages were also observed in lungs of CTL mice after ozone, along with CD11b(+)Ly6C(Lo) and mannose receptor (MR)(+) anti-inflammatory macrophages...
October 5, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
Claudia Cantoni, Francesca Cignarella, Laura Ghezzi, Bob Mikesell, Bryan Bollman, Melissa M Berrien-Elliott, Aaron R Ireland, Todd A Fehniger, Gregory F Wu, Laura Piccio
Myeloid-derived cells play important modulatory and effector roles in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells, composed of monocytic (MO) and polymorphonuclear (PMN) fractions, which can suppress T cell activities in EAE. Their role in MS remains poorly characterized. We found decreased numbers of circulating MDSCs, driven by lower frequencies of the MO-MDSCs, and higher MDSC expression of microRNA miR-223 in MS versus healthy subjects...
October 4, 2016: Acta Neuropathologica
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